In many individuals infected with human immunodeficiency virus (HIV), the immunosuppressive effects of the virus will be accompanied by another serious complication of profound neurological disease. The objectives of this proposal are to further develop and apply new polymerase chain reaction-based amplification methods for single cells and in situ hybridization to (1) define the types of cells in the CNS that harbor HIV genomes; and (2) determine the kind and relative abundancy of viral and cellular transcripts in infected and uninfected cells to gain insight into virus-host cell relationships and mechanisms of tissue damage. PCR in situ, in situ hybridization and double-label methods will be used to identify and enumerate all the types of cells in the CNS harboring HIV and determine whether infection is latent or productive. Similar methods will be used to map cellular and viral proteins that may be the mediators of CNS injury, such as the viral env gene products and the cytokines tissue necrosis factor and gamma interferon, to see if there is a quantitative and spatial correlation with the extent of neuropathology. This information should provide insight into how HIV damages the CNS as the foundations for improved treatment to prevent or ameliorate the effects of HIV on the CNS.
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